title: The reduced form of coenzyme Q10 decreases the expression of lipopolysaccharide-sensitive genes in human THP-1 cells.
abstract: Monocytes are key players in inflammatory processes that are triggered by lipopolysaccharide (LPS), the major outer membrane component of Gram-negative bacteria. The present study in human monocytic THP-1 cells was designed in order to identify LPS-inducible genes that are down-regulated by the reduced form of coenzyme Q(10) (ubiquinol, Q(10)H(2)). For this purpose, THP-1 cells were incubated with 10 μM Q(10)H(2) for 24 hours. Subsequently, cells were stimulated for 4 hours with 1 μg/mL LPS, and the resulting gene expression levels were determined using microarrays. Fourteen LPS-inducible genes were identified to be significantly (P ≤ .05) down-regulated by Q(10)H(2) pretreatment between a factor of 1.32 and 1.65. The strongest effect of Q(10)H(2) incubation was found for the nuclear receptor coactivator 2 gene (NCOA2). Gene ontology terms revealed for the Q(10)H(2)-sensitive genes an involvement in, e.g., signal transduction processes (centaurin, delta 1; NCOA2; pleckstrin and Sec7 domain containing 3; protein phosphatase 2, regulatory subunit B [B56], γ isoform), transcriptional regulation (NCOA2; POU domain, class 2, transcription factor 1; ETS variant gene 3), and cell proliferation pathways (hypothetical protein FLJ36090, epidermal growth factor receptor pathway substrate 15). In conclusion, we provide evidence in THP-1 cells that Q(10)H(2) modulates LPS-induced gene expression.
authors.affiliation: Molecular Prevention, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Kiel, Germany.
authors.forename: Constance
authors.initials: C
authors.lastname: Schmelzer
authors.forename: Christine
authors.initials: C
authors.lastname: Kohl
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
authors.forename: Frank
authors.initials: F
authors.lastname: Döring
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D014451:Ubiquinone; C024989:coenzyme Q10